N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

Visalli, Valeria; Muscoli, Carolina; Sacco, Iolanda; Sculco, Francesca; Palma, Ernesto; Costa, Nicola; Colica, Carmela; Rotiroti, Domenicantonio; Mollace, Vincenzo

doi:10.1186/1471-2202-8-106

Cited by 41 publications

(41 citation statements)

References 57 publications

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“…Glutamine is a trophic amino acid produced largely in astrocytes by a glutamine synthase mediated conversion of glutamate to glutamine. HIV infection, encephalitis, HIV-gp120, Tat, tumour necrosis factor α and interleukin-1β impair glutamate uptake [59,60], and gp120 is known to reduce glutamine levels and survival of cultured astrocytes [61]. Free radical scavenging with N -acetylcysteine protects astrocytes from gp120 and increases glutamine concentrations [61].…”

Section: Discussionmentioning

confidence: 99%

“…HIV infection, encephalitis, HIV-gp120, Tat, tumour necrosis factor α and interleukin-1β impair glutamate uptake [59,60], and gp120 is known to reduce glutamine levels and survival of cultured astrocytes [61]. Free radical scavenging with N -acetylcysteine protects astrocytes from gp120 and increases glutamine concentrations [61]. These data suggest that improvements in glial energetics may facilitate recovery of cognitive function by increasing uptake and conversion of glutamate to glutamine in patients with improving cognitive function.…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients

Dickens

Anthony

Deutsch

et al. 2015

Aids

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Objectives To identify prognostic surrogate markers for change in cognitive states of HIV-infected patients. Design Longitudinal cerebrospinal fluid (CSF) samples were collected from 98 HIV+ patients identified by temporal change in cognitive states classified as normal, stably impaired, improving and worsening. Methods The metabolic composition of CSF was analysed using 1HNMR spectroscopy that focused on energy metabolites. Metabolic biomarkers for cognitive states were identified using multivariate partial least squares regression modelling of the acquired spectra, combined with nonparametric analyses of metabolites with clinical features. Results Multivariate modelling and cross-validated recursive partitioning identified several energy metabolites that, when combined with clinical variables, classified patients based on change in neurocognitive states. Prognostic identification for worsening was achieved with four features that included no change in a detectable plasma viral load, elevated citrate and acetate; decreased creatine, to produce a model with a predictive accuracy of 92%, sensitivity of 88% and 96% specificity. Prognosis for improvement contained seven features that included first visit age less than 47 years, new or continued use of antiretrovirals, elevated glutamine and glucose; decreased myo-inositol, β-glucose and creatinine to generate a model with a predictive accuracy of 92%, sensitivity of 100% and specificity of 84%. Conclusion These CSF metabolic results suggest that worsening cognitive status in HIV-infected patients is associated with increased aerobic glycolysis, and improvements in cognitive status are associated with a shift to anaerobic glycolysis. Dietary, lifestyle and pharmacologic interventions that promote anaerobic glycolysis could protect the brain in setting of HIV infection with combined antiretroviral therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients

Dickens

Anthony

Deutsch

et al. 2015

Aids

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“…Considering that some authors have been suggested the use of antioxidants as agents which might reduce the incidence of oxidative stress as a consequence of infection or treatment and also it could impact on the development of other related diseases [63][64][65].…”

Section: Discussionmentioning

confidence: 99%

Multivariate discriminant analysis of redox and progression indexes in Cuban AIDS patients with Kaposis sarcoma

Valle¹,

Duque-Vizcaino²,

Calás-Hechavarria³

et al. 2017

Oxid Antioxid Med Sci

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Objectives: Infection by human immunodeficiency virus (HIV) generates sustained reactive oxygen species production. An increasing number of studies underline the pathogenic impact of high-grade local and systemic oxidative stress in the activation of Herpesvirus 8 producing Kaposi's sarcoma (KS) co-infection in acquired immunodeficiency syndrome (AIDS) patients. This study aimed to determine the redox status in AIDS-KS Cuban individuals and to explore the relation between redox and progression variables. Methods: Blood samples were drawn from 99 individuals divided into three groups (33 each one; age range 30-50 years): AIDS, AIDS-KS, and presumable healthy subjects. Total peroxide, malondialdehyde, and advanced oxidation protein products as damage indexes and antioxidant responses (glutathione, peroxidation potential, superoxide dismutase, and catalase) were determined from the blood samples. Furthermore, hematological and hemochemical indexes, progression indexes (viral load, CD4 + T lymphocyte absolute count), and tumoral progression indexes were assessed. Different statistical analyses were done. Results: Compared to healthy subjects, both groups of AIDS patients had significant differences in global indices of damage and antioxidant status. The comparison between the groups revealed that AIDS-KS group had a significantly higher damage and lower antioxidant status compared to the healthy control and AIDS groups. Multivariate statistical analysis clearly separated groups according progression indexes and redox profile, obtaining two canonical functions. Conclusions: These results corroborate that substantial oxidative stress occurs in AIDS condition and also during KS-HIV co-infection with different molecular extension and interdependence to progression indexes. Redox indexes diagnosis should be considered in early diagnostics, prevention and treatment of KS-HIV coinfection, which would be worthwhile to conduct a more comprehensive study and manage of infection.

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“…According to this principle a superoxid dismutase mimetic was able to protect against neuronal apoptosis induced by supernatants of HIV-infected M [240]. Antioxidants such as the glutathione precursor N-acetyl cystein (NAC) or derivatives thereof can prevent damage to a variety of cell types [241,242] but also inhibit viral reactivation induced by oxidative stress [243]. One report showed that CSF derived from HIV-infected patients mediates oxidative stress in neuronal cultures and that this effect can be inhibited by novel antioxidants such as Diosgenin or Ebselen [187].…”

Section: Targets For Adjunctive Therapymentioning

confidence: 99%

Complement and Microglia in the Neuropathogenesis of HIV Infection: Pro- and Anti-Inflammatory Aspects

Speth¹,

Rambach²,

Sopper³

2009

AIAAMC

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Viral penetration into the central nervous system (CNS) is an early event in the course of human immunodeficiency virus (HIV) pathogenesis and occurs in the vast majority of the infected individuals. Consequences are diverse symptoms of neurological dysfunction in a substantial proportion of patients, as well as the establishment of a lifelong viral reservoir. The severity of symptoms ranges from subclinical alterations in motor and cognitive functions termed HIV neurocognitive impairment (HNCI) to full blown HIV-associated dementia (HAD) in late stages of AIDS.The interaction of HIV with the cerebral immunity is an important aspect of the pathogenesis and has not yet been elucidated in detail. The blood-brain barrier strictly limits the access of peripheral immune elements, thus emphasising the role of the local innate immunity. The two central players of the antimicrobial campaign in the brain are complement and microglia. The complement system represents a fast-acting soluble cascade with a broad variety of antiviral effector mechanisms whereas microglia are the most potent cellular immune elements in the CNS. Both orchestrate a network of innate immune reactions that aim to limit HIV spreading. On the other hand, however, the inflammatory processes may exceed any reasonable limit and develop a dynamic that makes them contribute to the virus-induced neurological damage and dysfunctions.In the present article we describe profit, limitations and danger of the pro-inflammatory activities executed by complement and microglia in the HIV-infected brain. Furthermore we speculate about putative benefits of pro-inflammatory therapies to support the antiviral immune reaction, as well as of anti-inflammatory therapeutic approaches to avoid excessive inflammation and subsequent neurological lesions.

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N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

Cited by 41 publications

References 57 publications

Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients

Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients

Multivariate discriminant analysis of redox and progression indexes in Cuban AIDS patients with Kaposis sarcoma

Complement and Microglia in the Neuropathogenesis of HIV Infection: Pro- and Anti-Inflammatory Aspects

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